PUBLICATION
ERG potassium channels and T-type calcium channels contribute to the pacemaker and atrioventricular conduction in zebrafish larvae
- Authors
- Salgado-Almario, J., Molina, Y., Vicente, M., Martínez-Sielva, A., Rodríguez-García, R., Vincent, P., Domingo, B., Llopis, J.
- ID
- ZDB-PUB-231210-16
- Date
- 2023
- Source
- Acta physiologica (Oxford, England) 240(2): e14075 (Journal)
- Registered Authors
- Domingo Moreno, Beatriz, Llopis, Juan Francisco, Vicente Ruiz, Manuel
- Keywords
- ERG potassium channel, T-type calcium channel, atrioventricular block, calcium, heart, zebrafish
- MeSH Terms
-
- Animals
- Atrioventricular Block*
- Bradycardia
- Calcium Channels, T-Type*/physiology
- Ether-A-Go-Go Potassium Channels
- Heart Rate/physiology
- Humans
- Mammals
- Myocytes, Cardiac
- Pacemaker, Artificial*
- Transcriptional Regulator ERG
- Zebrafish
- PubMed
- 38071417 Full text @ Acta Physiol. (Oxf).
Citation
Salgado-Almario, J., Molina, Y., Vicente, M., Martínez-Sielva, A., Rodríguez-García, R., Vincent, P., Domingo, B., Llopis, J. (2023) ERG potassium channels and T-type calcium channels contribute to the pacemaker and atrioventricular conduction in zebrafish larvae. Acta physiologica (Oxford, England). 240(2):e14075.
Abstract
Aim Bradyarrhythmias result from inhibition of automaticity, prolonged repolarization, or slow conduction in the heart. The ERG channels mediate the repolarizing current IKr in the cardiac action potential, whereas T-type calcium channels (TTCC) are involved in the sinoatrial pacemaker and atrioventricular conduction in mammals. Zebrafish have become a valuable research model for human cardiac electrophysiology and disease. Here, we investigate the contribution of ERG channels and TTCCs to the pacemaker and atrioventricular conduction in zebrafish larvae and determine the mechanisms causing atrioventricular block.
Methods Zebrafish larvae expressing ratiometric fluorescent Ca2+ biosensors in the heart were used to measure Ca2+ levels and rhythm in beating hearts in vivo, concurrently with contraction and hemodynamics. The atrioventricular delay (the time between the start of atrial and ventricular Ca2+ transients) was used to measure impulse conduction velocity and distinguished between slow conduction and prolonged refractoriness as the cause of the conduction block.
Results ERG blockers caused bradycardia and atrioventricular block by prolonging the refractory period in the atrioventricular canal and in working ventricular myocytes. In contrast, inhibition of TTCCs caused bradycardia and second-degree block (Mobitz type I) by slowing atrioventricular conduction. TTCC block did not affect ventricular contractility, despite being highly expressed in cardiomyocytes. Concomitant measurement of Ca2+ levels and ventricular size showed mechano-mechanical coupling: increased preload resulted in a stronger heart contraction in vivo.
Conclusion ERG channels and TTCCs influence the heart rate and atrioventricular conduction in zebrafish larvae. The zebrafish lines expressing Ca2+ biosensors in the heart allow us to investigate physiological feedback mechanisms and complex arrhythmias.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping